Project description:Colorectal cancer is the third most common malignancy and the fourth most common cause of cancer mortality worldwide. In 2008, more than one million cases were newly diagnosed, and more than 600,000 people died from the disease. Given its slow development from removable precancerous lesions and curable early stages, screening for CRC has the potential to reduce both the incidence and mortality of the disease. However, compliance with current screening methods remains poor and there is a clear need for an accurate in vitro blood test to increase participation in colorectal cancer screening. In this study, we performed genome-wide gene expression profiling of peripheral blood samples from 100 healthy controls and 100 colorectal cancer patients using PAXgeneTM technology and Affymetrix GeneChip® microarrays. We show that monitoring gene expression in blood results in distinct transcriptional profiles between the controls and cancer patients. Thus, the microarray-based blood gene expression profiling holds great promise for developing novel biomarkers for colorectal cancer detection.
Project description:Cancer is the most common disease around the world and colorectal cancer is the second most common cancer. The early diagnosis of colorectal cancer is difficult and relies on invasive diag-nostic tools such as colonoscopy and tissue biopsy. Other non-invasive techniques such as fecal occult blood screening test (FOBT) are less sensitive and accurate. The advantage of FOBT together with high throughput technology such as metabolomics could provide the advantages of non-invasive tool and the effectiveness of detecting novel colorectal cancer markers. In this way, this work focuses on the novelty of using FOBT as samples to perform metabolomics analysis and its application on colorectal cancer population.
Project description:We found that low protein diet consumption resulted in decrease in the percentage of normal Paneth cell population in wild type mice, indicating that low protein diet could negatively affect Paneth cell function. We performed fecal microbiota composition profiling. Male mice were used at 4-5 weeks of age. Fecal samples were collected for microbiome analysis.
Project description:We found that western diet consumption resulted in decrease in the percentage of normal Paneth cell population in wild type mice, indicating that western diet could negatively affect Paneth cell function. Subsequent generations of western diet consumption further reduced percentages of normal Paneth cell population. We performed fecal microbiota composition profiling. Male mice were used at 4-5 weeks of age. Fecal samples were collected for microbiome analysis.
Project description:Microbiota dysbiosis and mucosa-associated bacteria are involved in colorectal cancer progression. We hypothesized that a time-specific interaction between dysbiotic pathobionts and host responses promote tumor growth. This study aimed to elucidate the dysfunctional host-microbe interplay in colon tumorigenesis by using a time-series metagenomics approach. A transient surge in fecal microbial richness was linked to a unique transcriptome profile in the mouse colon during carcinoma transformation. Monitoring gut microbiome may help identifying the window-of-opportunity to induce tumor regression using bacteria-targeted precision medicine.
Project description:Microbiota dysbiosis and mucosa-associated bacteria are involved in colorectal cancer progression. We hypothesized that a time-specific interaction between dysbiotic pathobionts and host responses promote tumor growth. This study aimed to elucidate the dysfunctional host-microbe interplay in colon tumorigenesis by using a time-series metagenomics approach. A transient surge in fecal microbial richness was linked to a unique transcriptome profile in the mouse colon during carcinoma transformation. Monitoring gut microbiome may help identifying the window-of-opportunity to induce tumor regression using bacteria-targeted precision medicine.
Project description:DNA methylation is an epigenetic mark that is altered in cancer and aging tissues. The effects of extrinsic factors on DNA methylation remain incompletely understood. Microbial dysbiosis is a hallmark of colorectal cancer, and infections have been linked to aberrant DNA methylation in cancers of the GI tract. To determine the microbiota’s impact on DNA methylation, we studied the DNA methylation of colorectal mucosa in germ-free (GF, no microbiome) and specific pathogen free (SPF, controlled microbiome) mice, as well as in interleukin 10 KO mice (Il10-/-) which are prone to inflammation and tumorigenesis in the presence of a microbiome. We compared DNA methylation changes to those seen in aging, and after exposure to the colon carcinogen azoxymethane (AOM). DNA methylation changes associated with aging were accelerated in the Il10-/- /SPF mice. By contrast, AOM induced profound hypomethylation that was distinct from the effects of aging or of the microbiome. CpG sites modified by the microbiome were over-represented among DNA methylation changes in colorectal cancer. Thus, the microbiome affects the DNA methylome of colorectal mucosa in patterns reminiscent of what is observed in colorectal cancer.
